Title : CYP26A1 knockout embryonic stem cells exhibit reduced differentiation and growth arrest in response to retinoic acid.

Pub. Date : 2008 Mar 15

PMID : 18241852






15 Functional Relationships(s)
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1 CYP26A1 knockout embryonic stem cells exhibit reduced differentiation and growth arrest in response to retinoic acid. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
2 CYP26A1, a cytochrome P450 enzyme, metabolizes all-trans-retinoic acid (RA) into polar metabolites, e.g. 4-oxo-RA and 4-OH-RA. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
3 CYP26A1, a cytochrome P450 enzyme, metabolizes all-trans-retinoic acid (RA) into polar metabolites, e.g. 4-oxo-RA and 4-OH-RA. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
4 CYP26A1, a cytochrome P450 enzyme, metabolizes all-trans-retinoic acid (RA) into polar metabolites, e.g. 4-oxo-RA and 4-OH-RA. 4-oxoretinoic acid cytochrome P450 family 26 subfamily A member 1 Homo sapiens
5 CYP26A1, a cytochrome P450 enzyme, metabolizes all-trans-retinoic acid (RA) into polar metabolites, e.g. 4-oxo-RA and 4-OH-RA. 4-oh-ra cytochrome P450 family 26 subfamily A member 1 Homo sapiens
6 CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a primary RA target gene, than Wt ES cells. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
7 CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a primary RA target gene, than Wt ES cells. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
8 CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a primary RA target gene, than Wt ES cells. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
9 CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a primary RA target gene, than Wt ES cells. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
10 CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a primary RA target gene, than Wt ES cells. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
11 CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a primary RA target gene, than Wt ES cells. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
12 Despite increased intracellular RA levels, CYP26a1(-/-) ES cells were more resistant than Wt ES cells to RA-induced proliferation arrest. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
13 Microarray analyses revealed that RA-treated CYP26A1(-/-) ES cells exhibited lower mRNA levels than Wt ES cells for genes involved in differentiation, particularly in neural (Epha4, Pmp22, Nrp1, Gap43, Ndn) and smooth muscle differentiation (Madh3, Nrp1, Tagln Calponin, Caldesmon1). Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
14 In contrast, genes involved in the stress response (e.g. Tlr2, Stk2, Fcgr2b, Bnip3, Pdk1) were expressed at higher levels in CYP26A1(-/-) than in Wt ES cells without RA. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens
15 Collectively, our results show that CYP26A1 activity regulates intracellular RA levels, cell proliferation, transcriptional regulation of primary RA target genes, and ES cell differentiation to parietal endoderm. Tretinoin cytochrome P450 family 26 subfamily A member 1 Homo sapiens